This study is a randomized, parallel group, placebo controlled, double-blind study using two doses of NAC. Subjects will receive placebo, NAC 600 mg, or NAC 1200 mg twice daily for eight weeks. We anticipate we will screen (by phone or in person) about 800 potential subjects. A total of 282 male and female subjects with cocaine dependence will be enrolled. The majority of these individuals will be recruited from the community and clinics. Recruitment will be through media advertisements, flyers, and by word-of-mouth.

The primary specific hypothesis of this study is: in treatment-seeking cocaine-dependent subjects, CBT with 600 mg or 1200 mg twice daily of NAC orally will have a significantly higher number of cocaine non-use days as compared to subjects receiving CBT coupled with placebo. Cocaine non-use days will be confirmed with three-times-a-week quantitative urine benzoylecognine levels and creatinine determinations. Subjects will be assessed on a number of biomedical and psychosocial variables known to influence cocaine treatment outcomes. These variables will be used in a stratification procedure to ensure a balanced distribution of these variables across all treatment groups.

Prior to beginning the study, individuals will receive oral and written information regarding the study and will sign an IRB-approved informed consent document, along with appropriate HIPAA forms. Prior to administration of study medications, each subject will receive a thorough medical history and physical, electrocardiogram, blood work including hematology and chemistry panel, urine drug screen for cocaine, and baseline rating instruments, including cue reactivity measures.

Once subjects have been on medication for two weeks, subjects will repeat the cue reactivity procedure. At the beginning of treatment phase, all subjects will receive manual-driven cognitive-behavioral therapy (CBT) weekly for eight weeks, administered by a Master''''s level therapist.

Inclusion Criteria:

• Dependent on cocaine and seeking treatment at the time of study enrollment
• Meets DSM IV criteria for cocaine dependence, as determined by a mini-SCID interview
• Currently uses cocaine by smoking, nasal or intravenous route of administration as confirmed by at least one positive urine screen for benzoylecgonine during the screening period prior to randomization
• Stable physical and mental health, as judged by interview and physical examinations

If female, have a negative pregnancy test and agree to use an adequate method of contraception for the duration of the study

• Live within a 50 mile radius of our research program and have reliable transportation

Exclusion Criteria:

• Current dependence, defined by DSM IV criteria, on any psychoactive substance other than cocaine, alcohol, nicotine, or marijuana or physiological dependence on alcohol requiring medical detoxification
• History of significant liver, kidney, endocrine, cardiac (i.e., arrhythmia requiring medication, angina pectoris, myocardial infarction,), stroke, seizure, neurological, non-drug-related psychiatric, gastrointestinal, pulmonary, hematologic or metabolic disorders, including homocysteinuria
• History of adverse reaction to cocaine including loss of consciousness, chest pain, psychosis, or seizure
• History of adverse reaction or hypersensitivity to NAC or drugs of the same class
• Significant active medical or psychiatric illness which might inhibit the ability to complete the study
• Active high blood pressure, as defined as a mean of three sitting blood pressure readings of 145/95 or higher within a ten-day period
• History of current or past asthma and/or the occasional or daily use of Albuterol or other beta-agonist inhalers
• Use of carbamazepine, phenytoin, nitrous oxide, methotrexate, 6 azauridine triacetate, or nitroglycerin within the last fourteen days or any other medication felt to be hazardous if taken with NAC
• Use of supraphysiologic doses of folate, cyanocobaltamine (B12), or pyridoxine (B6) that has been prescribed by a health care professional. Individuals taking supraphysiologic levels of these vitamins on a self-initiated basis may enter the study if they are willing to stop these vitamins beginning fourteen days prior to study and substitute a standard (study supplied) generic multiple vitamin with FDA-approved daily levels of these three vitamins. See Homocysteine section below
• Pregnant or breastfeeding
• Required by the court to obtain treatment for cocaine dependence
• Nnot seeking treatment for cocaine dependence
• Anticipating elective surgery or hospitalization within 20 weeks of enrollment
• Failure to have a consistent residence for the four weeks prior to enrollment
• History of childhood or adult seizures of any cause
• Participated in cocaine treatment (clinical or research) within 30 days of enrollment